Comprehensive N-Glycome Profiling of Cells and Tissues for Breast Cancer Diagnosis

Comprehensive N-Glycome Profiling of Cells and Tissues for Breast Cancer Diagnosis
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用于乳腺癌诊断的细胞和组织综合 N-糖分析

DOI:
10.1021/acs.jproteome.9b00073
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发表时间:
2019-06-01
影响因子:
4.4
通讯作者:
Yu, Guangli
Yu, Guangli
中科院分区:
生物学2区
文献类型:
--
作者:
Li, Qinying;Li, Guoyun;Yu, Guangli

文献摘要

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蛋白糖基化异常在包括不同癌症在内的多种疾病的进展中被观察到。在这项研究中,我们用PGC-ESI-MS/MS评估了人乳腺癌细胞和组织中不同的N-糖链模式。与乳腺上皮细胞相比,高甘露糖在乳腺癌细胞中显著增加。但N-糖链在组织中的变化比在细胞中的变化更明显。稳定地鉴定了63种不同的N-糖链,其中38种在癌旁组织和乳腺癌组织中表现出显著差异。乳腺癌组织中高甘露糖聚糖和岩藻糖化聚糖增加,而裂解聚糖和唾液酸聚糖减少。此外,共有27种N-聚糖在乳腺良性肿瘤和乳腺癌组织中显示出明显的差异,其中大多数包括二分糖和唾液酸糖在癌组织中的相对丰度降低。总体而言,三种高甘露糖N-葡聚糖(F0H6N2S0,F0H7N2S0,F0H8N2S0)在乳腺癌细胞和组织中都显示出显著的诊断准确性,表明它们在生物标记物中的潜在作用。此外,唾液酸聚糖与患者年龄呈负相关。综上所述,我们的结果可能有助于理解N-糖链在乳腺癌进展中的作用,并提出潜在的诊断生物标志物。
Aberrant protein glycosylation is observed in the progression of many types of diseases, including different cancers. In this study, we assess differential N-glycan patterns of human breast cancer cells and tissues by PGC-ESI-MS/MS. Compared with mammary epithelial cells, high-mannose glycans were significantly elevated in breast cancer cells. However, the alteration of N-glycans in tissues was more obvious than that in cells. Sixty-three kinds of different N-glycans were stably identified, and 38 types of them exhibited significant differences between paracarcinoma and breast cancer tissues. High-mannose glycans and core-fucosylated glycans were increased in the breast cancer tissues, while bisected glycans and sialylated glycans were decreased. Moreover, a total of 27 types of N-glycans displayed evident differences between benign breast tumor and breast cancer tissues, and most of them including bisected and sialylated glycans exhibited decreased relative abundances in cancer tissues. Overall, three high-mannose N-glycans (F0H6N2S0, F0H7N2S0, F0H8N2S0) exhibited significant diagnostic accuracy in both breast cancer cells and tissues, suggesting their potential role in biomarkers. Furthermore, a negative correlation between sialylated glycans and age of patients was identified. In conclusion, our results may be beneficial to understand the role that N-glycan plays on the progression of breast cancer and propose potential diagnostic biomarkers.